The Crusades

Reflective piece on the crusades.

Adeno-associated virus-8-Mediated intravenous transfer of myostatin propeptide leads to systemic functional improvements of slow but not fast muscle

Myostatin is a member of the transformating growth factor-_ (TGF-_) superfamily of proteins and is produced almost exclusively in skeletal muscle tissue, where it is secreted and circulates as a serum protein. Myostatin acts as a negative regulator of muscle mass through the canonical SMAD2/3/4 signaling pathway. Naturally occurring myostatin mutants exhibit a ‘double muscling’ phenotype in which muscle mass is dramatically increased as a result of both hypertrophy and hyperplasia. Myostatin is naturally inhibited by its own propeptide; therefore, we assessed the impact of adeno associated virus-8 (AAV8) myostatin propeptide vectors when systemically introduced in MF-1 mice. We noted a significant systemic increase in muscle mass in both slow and fast muscle phenotypes, with no evidence of hyperplasia; however, the nuclei-to- cytoplasm ratio in all myofiber types was significantly reduced. An increase in muscle mass in slow (soleus) muscle led to an increase in force output; however, an increase in fast (extensor digitorum longus [EDL]) muscle mass did not increase force output. These results suggest that the use of gene therapeutic regimens of myostatin inhibition for age-related or disease-related muscle loss may have muscle-specific effects.

Sequence heterogeneity of an mpb70 gene analogue in Mycobacterium kansasii

The protein antigen MPB70 is a major component of culture supernatants of Mycobacterium bovis and Is an active ingredient of bovine PPD used for skin-testing cattle for tuberculosis. we have shown that Mycobacterium kansasii possesses a similar gene that cross-reacts in a PCR test for M. bovis. Single strand conformational polymorphism analysis, and the DNA sequence of the PCR product, shows differences between M. kansasii strains, supporting the suggestion that M. kansasii is not a homogeneous species.

Relationships between yield and mineral concentrations in potato tubers

There is concern that modern cultivars and/or agronomic practices have resulted in reduced concentrations of mineral elements essential to human nutrition in edible crops. Increased yields are often associated with reduced concentrations of mineral elements in produce, and a number of recent studies have indicated that, when grown under identical conditions, the concentrations of several mineral elements are lower in genotypes yielding more grain or shoot biomass than in older, lower-yielding genotypes. Potato is a significant crop, grown worldwide, yet few studies have investigated whether increasing yields, through agronomy or breeding, affects the concentrations of mineral elements in tubers. This article examines the hypothesis that increasing yields, either by the application of mineral fertilizers and/or by growing higher-yielding varieties, leads to decreased concentrations of mineral elements in tubers. It reports that the application of fertilizers influences tuber elemental composition in a complex manner, presumably as a consequence of soil chemistry and interactions between mineral elements within the plant, that considerable variation exists between potato genotypes in the concentrations of mineral elements in their tubers, and that, like in other crops, higher-yielding genotypes occasionally have lower concentrations of some mineral elements in their edible tissues than lower-yielding genotypes.

Opportunistic assessment of hearing in elderly inpatients

Objective: To determine the prevalence of occult hearing loss in elderly inpatients, to evaluate feasibility of opportunistic hearing screening and to determine subsequent provision of hearing aids. Materials and methods: Subjects (>65 years) were recruited from five elderly care wards. Hearing loss was detected by a ward-based hearing screen comprising patient-reported assessment of hearing disability and a whisper test. Subjects failing the whisper test or reporting hearing difficulties were offered formal audiological assessment. Results: Screening was performed on 51 patients aged between 70 and 95 years. Of the patients, 21 (41%) reported hearing loss and 16 (31%) failed the whisper test. A total of 37 patients (73%) were referred for audiological assessment with 17 (33%) found to have aidable hearing loss and 11 were fitted with hearing aids (22%). Discussion: This study highlights the high prevalence of occult hearing loss in elderly inpatients. Easy two-step screening can accurately identify patients with undiagnosed deafness resulting in significant proportions receiving hearing aids.

Revolutionary insurgencies, paradigmatic cases

This essay will examine and compare the production of women's writing during and after the Nicaraguan and Cuban Revolutions, a corpus that includes novels, poetry, and testimonies, but also features considerable generic hybridity. Since both revolutions are separated by some twenty years, each must be understood in the context of the specific ideological conditions that framed women’s participation in culture and revolution, and must also be considered in light of evolving gender discourses, both national and international. As such, these texts respond to both local and transnational paradigms of feminine subjectivity, and highlight the particular problems that arise from women’s insertion into the revolution and its representation in literature. These writers also have to negotiate the evolving context of revolution itself, with its moments of euphoria and disenchantment – and it is here that the greatest contrasts can be found between the two revolutionary instances and their political features: whilst Cuba’s revolutionary process has somehow survived economic crisis and created a level of political stability and continuity (not without its own problems), the Nicaraguan case is characterised by ruptures and resentments which are clearly reflected in the work of writers before, during, and after the Sandinista revolution, and which continue to the present day. This chapter will address the work of the most prominent woman writer of the Nicaraguan revolution, Gioconda Belli, whose main work reflects her involvement in the Sandinista struggle; ex-commander Mónica Baltodano has recently compiled a four volume piece with testimonials of men and women who participated in the organization and actions led by the Frente Sandinista de Liberación Nacional, and Violeta Barrios de Chamorro, former president of Nicaragua, who has recently co-authored an autobiography. There are other women poets to consider, especially under the auspices of the Asociación de Mujeres Nicaraguenses Luisa Amanda Espinoza, such as Vidaluz Meneses, Michele Najlis and Daisy Zamora. The testimonios compiled by Margaret Randall are also important pieces to consider for both Nicaragua and Cuba. The most important voices of the Cuban revolution still resident on the island are poet Nancy Morejón and writers Mirta Yáñez and Aida Bahr, with younger writers such as Adelaida Fernández de Juan and Marilyn Bobes representing a more recent generation.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

A moving-point approach to model shallow ice sheets: a study case with radially symmetrical ice sheets

Predicting the evolution of ice sheets requires numerical models able to accurately track the migration of ice sheet continental margins or grounding lines. We introduce a physically based moving-point approach for the flow of ice sheets based on the conservation of local masses. This allows the ice sheet margins to be tracked explicitly. Our approach is also well suited to capture waiting-time behaviour efficiently. A finite-difference moving-point scheme is derived and applied in a simplified context (continental radially symmetrical shallow ice approximation). The scheme, which is inexpensive, is verified by comparing the results with steady states obtained from an analytic solution and with exact moving-margin transient solutions. In both cases the scheme is able to track the position of the ice sheet margin with high accuracy.

Transdural motor cortex stimulation reverses neuropathic pain in rats: A profile of neuronal activation

Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos-IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos-IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain. (c) 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression

Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We, therefore, generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse to test this hypothesis. At 12 wk of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80 mmHg plus 1 mu M epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase vs. the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, whereas cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure and modest mitochondrial dysfunction in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression.